FIGUREFIGUREFigure: Robert Y. Osamura, MDFigure: Guillermo A. Herrera, MDImmunohistochemistry and electron microscopy have been utilized for the diagnosis of not only neoplastic diseases but also non-neoplastic lesions. The former application is far more common (the previous issue of Pathology Case Reviews was devoted to it) with one very notable exception: medical renal conditions. The use of electron microscopy and immunofluorescence (conceptually replacing immunohistochemistry) techniques in the evaluation of medical renal diseases makes this the most widely used application of electron microscopy and immunofluorescence techniques in diagnostic pathology. Since issues of Pathology Case Reviews addressing renal pathology have been previously published, the current issue will not cover this most important application. An important role for ultrastructural and immunohistochemical evaluation in selec-ted non-neoplastic conditions remains noteworthy. Among the general categories of conditions in which these ancillary techniques may play an important role are the following: (1) inflammatory diseases, (2) metabolic disorders, (3) storage conditions, (4) infectious processes, and (5) reactive endocrine disorders, among others. Inflammatory cells and their cytokines play a fundamental role in the etiopathogenesis of inflammatory bowel diseases. Dr. Nagura discusses how these ancillary techniques have contributed to our understanding of these conditions leading to more accurate diagnosis and overall better conceptualization. Metabolic diseases continue to present significant challenges to the pediatric pathologists and use of the proper ancillary diagnostic techniques is very important in the work-up of these cases. Dr. Hicks addresses in his article the complementary roles of immunohistochemistry and electron microscopy in the diagnosis and evaluation of alpha −1 antitrypsin deficiency. The evaluation of non-neoplastic neurologic conditions is sometimes complicated by the quality of the material submitted for evaluation, which may suboptimal. Dr. Fowler highlights how this material can be examined using ancillary diagnostic techniques providing key information influencing patients’ management which could not be obtained from light microscopic evaluation alone. Dr. Tsutsumi et al. address the diagnosis of acanthamebic meningoencephalitis and demonstrate in this article the usefulness of indirect immunoperoxidase staining using the patient’s own serum in making the correct diagnosis. Dr. Howell et al. discuss the utilization of ancillary diagnostic techniques in the diagnosis of polyoma virus, an extremely important etiologic agent responsible for renal dysfunction in immunosuppressed transplant patients. Finally, Dr. Kumaki et al. demonstrate a couple of cytoplasmic inclusions in non-neoplastic neuroendocrine cells using complementary ancillary diagnostic techniques and their importance in diagnosis. These contributions highlight the importance and usefulness of the combined use of immunohistochemistry and electron microscopy in the current practice of diagnostic pathology. Plutarch, Greek author, moral philosopher, and biographer once said: “Medicine to produce health, has to examine disease.” Pathologists examine and scrutinize diseases in their efforts to make the correct diagnosis and obtain useful information impacting on patients’ management and determination of prognosis. The scrutiny must not fall short of accomplishing what is every pathologist’s goal: to reach the degree of accuracy that is needed to provide the patient with a definitive and accurate assessment of the pathologic process upon which to base clinical management and therapeutic decisions. Electron microscopy and immunohistochemistry together with other ancillary techniques such as flow-cytometry and molecular techniques must join forces to aid pathologists in their quest for the right diagnosis. The presentations in this issue of Pathology Case Reviews clearly illustrate that these techniques can work together in accomplishing just that. Undoubtedly, proper utilization of ancillary diagnostic techniques enhances pathologic evaluation. As an important corollary, proper preservation of the material for ultrastructural evaluation must remain a priority. There is nothing more disappointing that realizing the need for electron microscopy to resolve a diagnostic dilemma and to have to use paraffin-embedded tissue with suboptimal preservation. As a consequence, the diagnosis may be compromised. The alternative, which is to put the patient through another invasive procedure to obtain additional material, is also unacceptable. The need for ancillary diagnostic techniques must be anticipated. The cases requiring a sophisticated diagnostic approach may be few and most general pathology laboratories may not be ready to tackle many of these unusual diagnostic problems. For example, while immunohistochemistry is currently available in most surgical pathology laboratories, the antibodies that may be needed to address the diagnostic problem may not be in the inventory of that particular laboratory. Furthermore, electron microscopy may be required and this may necessitate sending the case out to a laboratory with state-of-the-art electron microscopic diagnostic services. It may also be the case that the pathologist may want a consultation from an expert in the field who can select the combination of diagnostic techniques that may be needed to answer the question. Because of all these reasons, pathologists must remain alert to possible diagnostic requirements of various clinical situations.